Ibrutinib, an inhibitor of Bruton's tyrosine kinase, is approved in United States for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, and lymphoplasmacytic lymphoma (U.S. Pat. No. 7,514,444, U.S. Pat. No. 7,718,662, and U.S. Pat. No. 8,735,403). The recommended dose of ibrutinib is 420 to 560 mg orally once daily. However, the absolute bioavailability of ibrutinib in fasted humans (n=8) was 2.9% (90% CI=2.1-3.9) and doubled when combined with a meal (European Medicines Agency).
The need for higher ibrutinib dosage to counter its low oral bioavailability may be responsible for adverse side effects such as nausea or emesis, dizziness and diarrhea. Moreover, the low oral bioavailability may result in variable absorption and therapeutic response.